This R-21 proposal is in response to NIAAA PA-03-132 for studies to conduct secondary analyses of existing alcohol and HIV/AIDS data sets with the goal of advancing knowledge about the relationship between alcohol use and the progression and treatment of HIV/AIDS. The Johns Hopkins HIV Clinical Cohort is an investigator-initiated longitudinal observational cohort of patients who receive primary HIV/AIDS care on the Johns Hopkins AIDS Service. The Cohort was established in 1991, and has provided a rich source of data for over 200 papers and abstracts that have examined the natural history, treatment and outcomes of HIV infection in patients in care. It has been supported principally with federal funds. As part of this cohort study, we developed an audio computer-assisted self-interview (A-CASI) to assess antiretroviral adherence and alcohol and substance use. The A-CASI approach has been shown to enhance the validity of the self-report of sensitive behaviors. This approach has been well-accepted by our patients with over 4500 interviews conducted on almost 2000 patients over the past 5 years, and several analyses of adherence and treatment response conducted and published. To date, we have not made more than minimal use of the data we have collected on alcohol use and abuse. This includes data from our A-CASI, and also data abstracted from medical records of physicians, nurses and social workers/case managers, and electronic data on inpatient, ambulatory and alcohol treatment utilization. By linking our existing alcohol use data and clinical HIV/AIDS data, we propose to address the following specific aims: 1) Evaluate the effect of hazardous alcohol use on HIV disease progression, by determining the effect of alcohol use on virologic and immunologic response to antiretroviral therapy, on development of opportunistic infections that accompany HIV infection, on survival with HIV infection, and the effect on development of HIV resistance mutations that limit the effective choices available for treatment, and increase the risk of transmitting resistant HIV to others. 2) Evaluate the effect of hazardous alcohol use on prescribing of and adherence to antiretroviral therapy. We believe that our research will yield valuable results to better understand the relationship between alcohol use and HIV/AIDS.